Radiotherapy system, method for delivering neutron receptors, and method for treating or diagnosing cancer

Abstract

A radiotherapy system comprises a neutron acceptor, an atomization device for aerosolizing the neutron acceptor and an energy beam generator. The invention relates to a use of an aerosolized neutron receptor for preparing a medicament for treating cancer in an individual irradiated by neutrons. Use of an aerosolized radiopharmaceutical for the preparation of a medicament for diagnosing cancer in a subject in need thereof, comprising administering to the subject an effective amount of the radiopharmaceutical and receiving an energy beam signal from the subject. A method for delivering a neutron receptor to an individual during radiation therapy comprises aerosolizing the neutron receptor and administering an effective amount of the neutron receptor to the individual.

Description

[Technical field]

[0001] The present disclosure relates to radiation therapy and, more particularly, to neutron capture therapy. [Background technology]

[0002] Boron neutron capture therapy (BNCT) is a targeted radiotherapy that uses the high absorption characteristics of tumor cells to boron-10 drugs. Tumor cells that absorb boron-10 drugs tend to capture neutrons and undergo high-energy nuclear fission reactions ( 10 B(n,α) 7 Li), releases high-linear energy transfer particles: α particles ( 4 He), lithium particles ( 7 Li) and an energy of about 2.4MeV. The movement distance of these high linear energy transfer particles is about 10μm, which is close to the cell diameter, so they can directly cause fatal damage to the DNA of tumor cells. On the contrary, other tissues in the body composed of basic elements such as carbon, hydrogen, oxygen and nitrogen are not easy to capture neutrons. This property enables BNCT to create a significant dose gradient between tumor cells and normal cells. This is beneficial for treating local recurrent tumors that are difficult to irradiate or have unclear boundaries with normal tissues, thereby minimizing damage to healthy tissues and providing patients with less harmful treatment.

[0003] The high accumulation of boron-10 drugs and their selective delivery to tumor cells are the key to improving the therapeutic effect of BNCT and avoiding damage to adjacent healthy cells. According to the current clinical standards for BNCT, the tumor-to-normal tissue ratio (T / N ratio) of boron-10 drugs must be greater than 2.5 on average. However, during clinical BNCT treatment, boron-10 delivery agents are usually injected intravenously into patients, and these low molecular weight compounds are easily eliminated from tumor cells and blood, resulting in a poor T / N ratio.

[0004] Therefore, there is still an urgent need in the art to improve the T / N ratio of boron reagents and expand the application of BNCT. [Summary of the invention]

[0005] In view of the above problems, the present disclosure provides a radiotherapy system, which includes a neutron acceptor, an atomizer and an energy beam generator, wherein the atomizer is used for aerosolizing the neutron acceptor.

[0006] The present disclosure further provides a use of a neutron receptor for preparing a drug for treating cancer in an individual in need thereof. The neutron receptor is aerosolized and contains an element that can be triggered or activated by neutron irradiation, and the individual is neutron irradiated.

[0007] The present disclosure further provides a use of a radioactive agent for preparing a drug for diagnosing cancer, which comprises: administering an effective amount of aerosolized radioactive agent to an individual in need; and receiving an energy beam signal from the individual.

[0008] The present disclosure further provides a method for delivering neutron receptors to an individual during radiation therapy, comprising: aerosolizing the neutron receptors; and administering an effective amount of the neutron receptors to the individual. The neutron receptors contain an element that can be triggered or activated by neutron irradiation.

[0009] By aerosolizing and administering to an individual, the present disclosure can significantly increase the T / N ratio of the individual's neutron receptors to improve the effect of radiation therapy or diagnosis and avoid damage to healthy cells.

Brief Description of the Drawings

[0010] The present disclosure will be more readily understood by referring to the following description in conjunction with the accompanying drawings. Figure 1 A lung tumor animal model according to at least one embodiment of the present disclosure is shown. Figure 2 The delivery process of the boron-phenylalanine-fructose complex (BPA-Fr) of at least one embodiment of the present disclosure is shown. Symbols in the figure 1: container; 2: holder; 3: nasal cavity; 4: drug; 5: atomization device. Figure 3A Shown are the concentrations of boron-10 in tumor and normal tissues 5, 10, and 15 minutes after inhalation administration of aerosolized BPA-Fr in tumor-bearing mice and non-tumor-bearing (normal) mice. Figure 3B The boron-10 uptake (tumor / normal tissue ratio) in mice not administered with BPA-Fr (control group), 15 minutes after intraperitoneal injection (IP 15), 5 minutes after inhalation administration (Inhale 5), 10 minutes after inhalation administration (Inhale 10), and 15 minutes after inhalation administration (Inhale 15) are shown. Figure 3C Shown are the concentrations of boron-10 in tumor tissue and blood 5, 10, and 15 minutes after inhalation administration of aerosolized BPA-Fr in tumor-bearing mice and non-tumor-bearing (normal) mice. Figure 3DThe boron-10 uptake (tumor / blood ratio) in mice not administered with BPA-Fr (control group), 15 minutes after intraperitoneal injection (IP 15), 5 minutes after administration by inhalation (Inhale 5), 10 minutes after administration by inhalation (Inhale 10), and 15 minutes after administration by inhalation (Inhale 15) are shown. [Specific implementation method]

[0011] The following embodiments are provided to illustrate the present disclosure in detail. After reading the present disclosure, a person with ordinary knowledge in the art can easily understand the advantages and effects of the present disclosure, and can implement or apply in other different embodiments. Therefore, the following embodiments for implementing the present disclosure can be modified and / or changed without violating the scope of its different aspects and applications, and any component or method within the scope of the present disclosure can be combined with any other component or method disclosed in any embodiment of the present disclosure.

[0012] As used herein, the articles "a", "an" and "the" refer to one or to more than one (ie, to at least one) of the grammatical objects of the article, unless expressly stated otherwise, and the term "or" is used interchangeably with the term "and / or", unless expressly stated otherwise.

[0013] As used herein, the phrase "at least one" refers to one or more components and should be understood to mean at least one component selected from any one or more components in the listed components, but does not necessarily include at least one of each component listed in the listed components, and does not exclude any combination of elements in the listed elements. This definition also allows that components may optionally exist in addition to the components identified in the list of components referred to by the phrase "at least one", whether related or unrelated to the identified components. Thus, as a non-limiting example, "at least one of A and B" (or, equivalently, "at least one of A or B", or, equivalently, "at least one of A and / or B") may refer in one embodiment to at least one A, optionally including more than one A, without B (and optionally including components other than B); in another embodiment, to at least one B, optionally including more than one B, without A (and optionally including components other than A); in yet another embodiment, to at least one A, optionally including more than one A, and at least one B, optionally including more than one B (and optionally including other components).

[0014] As used herein, the terms "include", "comprising", "including" and any other variations thereof are intended to cover non-exclusive inclusions. For example, when describing that something "includes" a limitation, unless otherwise stated, it may additionally include other components, components, parts, structures, regions, parts, devices, systems, steps or connections, etc., and other limitations should not be excluded.

[0015] The numerical range used herein is inclusive and combinable, and any numerical value falling within the numerical range herein can be regarded as a maximum or minimum value, to derive a sub-range therefrom. For example, the numerical range "10ppm to 200ppm" includes any sub-range between the minimum value 10ppm and the maximum value 200ppm, such as the sub-ranges from 10ppm to 50ppm, from 150ppm to 200ppm, from 30ppm to 80ppm, etc. In addition, the plurality of numerical values ​​used herein can be selected as the maximum and minimum values ​​as needed to derive the numerical range. For example, the numerical ranges of 20ppm to 40ppm, 20ppm to 60ppm, and 40ppm to 60ppm can be derived from the numerical values ​​of 20ppm, 40ppm, and 60ppm.

[0016] As used herein, the term "about" generally refers to a numerical value that encompasses a variation of ±20%, ±10%, ±5%, ±1%, ±0.5%, or ±0.1% from a numerical value or range. Such variation in numerical values ​​may occur due to, for example, experimental error, typical errors in measurement or processing procedures for making compounds, compositions, concentrates, or formulations, differences in the source, manufacture, or purity of the starting materials or components used in the present disclosure, or similar considerations. Alternatively, the term "about" means within the acceptable mean standard deviation when considered by one of ordinary skill in the art. Unless otherwise expressly stated, all numerical ranges, amounts, values, and percentages disclosed herein, such as amounts of material, duration of a time period, temperature, operating conditions, ratios of amounts, etc., should be understood to be modified by the term "about" in all cases.

[0017] As used herein, the term "treatment" refers to obtaining a desired pharmacological or physiological effect, such as partially or completely preventing, improving, alleviating or controlling a disease-related disorder, symptom or condition. The term "treatment" as used herein may refer to the application or administration of at least one therapeutic agent or method to an individual having a disease-related disorder, symptom or condition, with the purpose of partially or completely improving, alleviating, relieving, relieving, delaying the onset of at least one disease-related disorder, symptom or condition, reducing its severity, inhibiting its progression or reducing its incidence. In some embodiments, treatment may be administered to an individual who exhibits only early signs of such a disease, symptom or condition associated with the disease, with the purpose of reducing the risk of developing the same disease, but the present disclosure is not limited thereto.

[0018] As used herein, the term "diagnosis" refers to the classification or identification of a disease or condition molecularly or pathologically. In some embodiments, "diagnosis" may refer to the identification of a particular type of cancer, such as, but not limited to, lung cancer.

[0019] As used herein, the terms "subject" and "patient" are interchangeable and refer to animals, such as mammals. The term "subject" is intended to refer to males and females unless one gender is specifically indicated. In at least one embodiment of the present disclosure, the subject is a rodent, mouse, monkey, dog, cat, cow, horse, emu, sheep, deer, wolf, fox, pig, rabbit, chicken, ostrich, or human, but the present disclosure is not limited thereto. In some embodiments, the subject is a human.

[0020] As used herein, the term "effective amount" refers to the amount of an active agent or pharmaceutical composition sufficient to prevent, treat or diagnose a specific disease, symptom or condition associated with a disease in a desired individual. In some embodiments, the effective amount may vary by one of ordinary skill in the art and may depend on the use of excipients, the route of administration, the possibility of co-use with other therapeutic treatments and / or the condition to be treated.

[0021] As used herein, the term "administer" or "administering" refers to introducing an active ingredient into an individual by a method or route so that at least a portion of the active ingredient is localized in a desired location to produce a desired effect. For example, the active ingredient of the present disclosure can be administered to an individual by inhalation, but the present disclosure is not limited thereto.

[0022] As used herein, the term "pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, vehicle or composition, such as a solid or liquid filler, binder, diluent, preservative, biocompatible solvent, disintegrating agent, lubricant, suspending agent, flavoring agent, encapsulating material, thickener, acid, surfactant, complexing agent, wetting agent or any combination thereof. In some embodiments, each component is "pharmaceutically acceptable" in the sense of being compatible with other ingredients of the pharmaceutical formulation and suitable for contact with organs or tissues of an individual (e.g., but not limited to, a mammal) without excessive toxicity, allergic response, irritation, immunogenicity or other complications or problems. See, e.g., Remington: The Science and Practice of Pharmacy, 22nd ed.; Allen, ed.: Philadelphia, PA, 2012; Handbook of Pharmaceutical Excipients, 7th ed.; Rowe et al., eds.; Pharmaceutical Press and American Pharmaceutical Association: 2012; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash, eds.; Gower Publishing Company: 2007; Pharmaceutical Preformulations and Formulations, 2nd ed.; Gibson, ed.; CRC Press LLC: Boca Raton, FL, 2009.

[0023] In at least one embodiment of the present disclosure, a method for treating cancer is provided, comprising: administering an effective amount of an aerosolized neutron receptor to a subject in need thereof; and irradiating the subject with neutrons. In at least one embodiment of the present disclosure, a pharmaceutical composition for treating cancer in a subject in need thereof is provided, comprising: an effective amount of an aerosolized neutron receptor and a pharmaceutically acceptable carrier thereof, and the subject is irradiated with neutrons.

[0024] In at least one embodiment of the present disclosure, a method for diagnosing cancer is provided, comprising: administering an effective amount of an aerosolized radioactive agent to a subject in need thereof; and receiving an energy beam signal from the subject. In at least one embodiment of the present disclosure, a pharmaceutical composition for diagnosing cancer in a subject in need thereof is provided, comprising: an effective amount of an aerosolized radioactive agent and a pharmaceutically acceptable carrier thereof.

[0025] In at least one embodiment of the present disclosure, the cancer may be lung cancer. In some embodiments, the lung cancer may be selected from the group consisting of non-small cell lung cancer, small cell lung cancer, Pancoast tumor, bronchial tumor, pleuropulmonary blastoma, lung carcinoid tumor, and any combination thereof, but the present disclosure is not limited thereto. In some embodiments, the small cell lung cancer may be selected from the group consisting of adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and any combination thereof, but the present disclosure is not limited thereto.

[0026] In at least one embodiment of the present disclosure, the neutron acceptor may contain an element that can be triggered or activated by neutron irradiation. In some embodiments, the neutron acceptor may be labeled with a radioactive radionuclide. In some embodiments, the neutron acceptor may be a boron source or a gadolinium source. In some embodiments, the boron source can be selected from boronophenylalanine, sodium borocaptate, ammonia-carboxy-borane, sodium borate, borane salt, copper tetracarboranyltetraphenylporphyrin, o-carboranylalanine, boron-rich porphyrin conjugate, boron-containing nucleoside, boron-containing oligonucleotid, boron antibody conjugate, boron containing thiouracil derivative, boron containing methionine analog, boronated pyridine base, boronated purine base. base) and at least one of the group consisting of derivatives or isomers thereof, but the present disclosure is not limited thereto. In some embodiments, the boron source can be selected from boronophenylalanine-fructose complex (BPA-Fr), boronophenylalanine, para-boronophenyalanine, meta-boronophenyalanine, ortho-boronophenyalanine, 18 F-labeled borylphenylalanine ( 18 F-labeledboronophenyalanine), 18 F-labeled para-borylphenylalanine ( 18 F-labeled para-boronophenyalanine), 18F-labeled borylphenylalanine ( 18 F-labeled meta-boronophenyalanine), 18 F-labeled o-borylphenylalanine ( 18 F-labeled ortho-boronophenyalanine), borylphenylalanine-amidoalkyl dodecaborate At least one of the group consisting of boronophenylalanine-amide alkyl dodecaborate and amide of boronophenylalanine, but the present disclosure is not limited thereto.

[0027] In at least one embodiment of the present disclosure, the radioactive agent may include a 18 F. 15 O. 13 N. 11 C. 67 Ga, 99m Tc, 123 I. 124 I. 125 I. 131 I. 201 Tl and 111 In is a group of radionuclides (radionuclide), but the present disclosure is not limited thereto. In at least one embodiment of the present disclosure, the radioactive agent may include a neutron acceptor labeled by a radionuclide, for example: the radioactive agent may include a boron source labeled by a radionuclide or a gadolinium source labeled by a radionuclide, but the present disclosure is not limited thereto.

[0028] In at least one embodiment of the present disclosure, the effective amount may be a blood concentration of about 10 ppm to about 200 ppm, for example, a blood concentration of about 20 ppm to about 40 ppm, a blood concentration of about 50 ppm to about 170 ppm, or a blood concentration of about 60 ppm to about 100 ppm. In some embodiments, the effective amount may be a blood concentration of about 10 ppm, 20 ppm, 30 ppm, 40 ppm, 50 ppm, 60 ppm, 70 ppm, 80 ppm, 90 ppm, 100 ppm, 110 ppm, 120 ppm, 130 ppm, 140 ppm, 150 ppm, 160 ppm, 170 ppm, 180 ppm, 190 ppm, or 200 ppm, but the present disclosure is not limited thereto.

[0029] In at least one embodiment of the present disclosure, the effective amount may be about 0.1 mg / kg to about 500 mg / kg, for example, about 0.2 mg / kg to about 1 mg / kg, about 10 mg / kg to about 50 mg / kg, about 100 mg / kg to about 200 mg / kg, or about 300 mg / kg to about 400 mg / kg, but the present disclosure is not limited thereto. In some embodiments, the effective amount may be about 0.1 mg / kg, 1 mg / kg, 5 mg / kg, 10 mg / kg, 20 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, 100 mg / kg, 150 mg / kg, 200 mg / kg, 250 mg / kg, 300 mg / kg, 350 mg / kg, 400 mg / kg, 450 mg / kg, or 500 mg / kg, but the present disclosure is not limited thereto.

[0030] In at least one embodiment of the present disclosure, the energy beam generator may be a neutron beam generator.

[0031] In at least one embodiment of the present disclosure, the atomizing device may be a pharmaceutically acceptable atomizer, nebulizer, inhaler or compressor, but the present disclosure is not limited thereto. In some embodiments, the nebulizer may be a vibrating mesh nebulizer (VMN).

[0032] In at least one embodiment of the present disclosure, the neutron receptor may be administered to the respiratory system of a subject. In some embodiments, the respiratory system may contain the respiratory tract or lungs. In some embodiments, the respiratory system may contain the oral cavity, nasal cavity, pharynx, larynx, trachea, carina, primary bronchi, secondary bronchi, tertiary bronchi, bronchioles, alveoli, or any combination thereof.

[0033] In at least one embodiment of the present disclosure, the neutron acceptor may be administered by inhalation.

[0034] In at least one embodiment of the present disclosure, the administration time may be about 1 to 20 minutes, such as but not limited to: about 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 11 minutes, 12 minutes, 13 minutes, 14 minutes, 15 minutes, 16 minutes, 17 minutes, minutes, 18 minutes, 19 minutes, 20 minutes. In some embodiments, the inhalation administration time may be about 5 to 10 minutes, 6 to 8 minutes, 2 to 5 minutes, but the present disclosure is not limited thereto.

[0035] In at least one embodiment of the present disclosure, the neutron acceptor can be aerosolized by a pharmaceutically acceptable nebulizer, sprayer, inhaler or compressor.

[0036] In at least one embodiment of the present disclosure, the individual may suffer from lung cancer.

[0037] In at least one embodiment of the present disclosure, a method for delivering neutron receptors to a subject during radiation therapy further comprises irradiating the subject with neutrons.

[0038] In at least one embodiment of the present disclosure, the aerosolized neutron acceptor may be administered to the respiratory system of a subject by inhalation.

[0039] In at least one embodiment of the present disclosure, the radiation therapy may be neutron capture therapy. In some embodiments, the neutron capture therapy may be boron neutron capture therapy.

[0040] In at least one embodiment of the present disclosure, compared to other administration methods or dosage forms, administering aerosolized neutron receptors or aerosolized radioactive agents to an individual can significantly increase the T / N ratio of the individual's neutron receptors, and achieve relatively high neutron receptor accumulation in tumors and relatively low neutron receptor accumulation in normal cells or blood in a very short time (for example, but not limited to 5 to 10 minutes), thereby improving the effect of radiotherapy or diagnosis and avoiding damage to healthy cells. In some embodiments, a preferred administration method is inhalation administration, for example: inhaling aerosolized neutron receptors or aerosolized radioactive agents through the individual's mouth or nose, but the present disclosure is not limited thereto.

[0041] In at least one embodiment of the present disclosure, the present disclosure shows a higher T / N ratio of a boron source in an individual compared to the minimum T / N ratio required for clinical treatment. Therefore, the present disclosure can significantly increase the T / N ratio of a boron source in an individual to improve the therapeutic effect of BNCT and avoid damage to healthy cells. However, the present disclosure is not limited to boron sources, and in other embodiments, other neutron acceptors and neutron capture therapy also have similar excellent effects.

[0042] The following examples further demonstrate the efficacy of the present disclosure, but do not limit the scope of the present disclosure. Example

[0043] The present invention is further described by the following examples. However, these examples are only used to illustrate the present disclosure and are not intended to limit the scope and significance of the present disclosure in any way. In fact, many modifications and variations of the present disclosure will be clear to those skilled in the art after reading the present disclosure, and many modifications and variations of the present disclosure can be made without departing from the scope thereof.

[0044] Materials and Methods

[0045] Lung tumor animal model

[0046] animal

[0047] Male BALB / c nude mice (average weight 25 g) aged 6 to 8 weeks were used. The mice were housed in a pathogen-free environment at a temperature of 21±2° C. and a relative humidity of 30% to 70% in an animal center and were fed by dedicated personnel.

[0048] Tumor formation

[0049] A549 (adenocarcinoma) cells were maintained in Ham's F-12K medium containing 10% FBS (90% Ham's F-12K and 10% FBS) and 1% penicillin. 4 / 1μl) cells and suspended in Ham's F-12K. Before injection, cells and matrigel were mixed in a 1:1 ratio and kept on ice until injection. For injection, the cell mixture was gently mixed and transferred to a 30μl syringe equipped with a 30-gauge needle. The syringe was loaded onto a stereotaxic injection system and 20μl of the cell mixture was injected into each mouse.

[0050] Mice were anesthetized with isoflurane and the fur covering the left chest was shaved. Then, the mice were placed in a lateral position with the left chest facing up, and a small incision (0.5 to 1 cm) was made on the skin just below the shoulder blade. Next, the chest wall muscles were gently spread until the intercostal space and pleura were clearly visible. Then, the ribs were counted upward from the lower edge of the thorax to determine the tumor injection site between the fourth and fifth ribs of the posterior axillary line. At this stage, the syringe was gently advanced until its tip precisely contacted the intercostal space. The syringe was advanced 3.5 to 4.0 mm in the lung parenchyma and the tumor cell mixture was injected. After the cells were injected, the syringe was pulled out from the tissue and the covering muscles and skin were closed.

[0051] like Figure 1 As shown, two weeks after the injection of A549 cells, the chest cavity was opened and the growth of a tumor (orange arrow) in the left lung was seen.

[0052] Delivery of aerosolized BPA

[0053] An appropriate volume of BPA-Fr was drawn using a 5 mL syringe and then passed through a 13-mm Acrodisc syringe filter (Pall Life Sciences, Ann Arbor, USA) containing a 0.2 μm ultrafiltration membrane to remove any ice crystals present in the liquid drug.

[0054] like Figure 2As shown in step S101, after the mouse is anesthetized with isoflurane, the mouse is placed in a specially designed container 1, such as a restraint chamber, with only the nose exposed in the Aerochamber. Figure 2 As shown in step S102, the container 1 is connected to the holder 2 (such as but not limited to the valve holding chamber (VHC)), and the connection is sealed with a single-layer sealing film. Figure 2 The atomization device 5 (such as but not limited to a vibrating mesh nebulizer (VMN)) with the BPA-Fr drug 4 shown in step S103 effectively prevents aerosol backflow and exposes the mouse nasal cavity 3.

[0055] The calculated dose of filtered BPA-Fr was placed in the medicine cup of the VMN at a concentration of 13 μL per gram. The power was then turned on and the drug was manually administered for 5 seconds, followed by a 30-second pause to ensure that the mouse had enough time to inhale the drug. When the drug was administered and there was no more mist in the device, the inhalation treatment was considered complete. Next, 100 μL of phosphate-buffered saline was injected into the medicine cup and continued to be aerosolized for inhalation by the mouse to reduce drug residue in the cup.

[0056] Analysis of BPA concentration using mass spectrometry

[0057] Injection 10 5 A549 cells 2 weeks later, the boron compound administration regimen was evaluated in 2 mice. BPA-Fr was administered by inhalation at a dose of 0.3 mg BPA / g body weight.

[0058] Two hours after the administration of the boron compound, the animals were immediately sacrificed by overdose anesthesia for tissue sampling. Blood samples were collected by cardiac puncture. The right lung of each mouse was collected as normal tissue, while the left lung showing visible tumor nodules was removed and collected. The collected tissue and blood samples were dissolved in 10% nitric acid for subsequent measurement of boron-10 using ICP-MS.

[0059] in conclusion

[0060] In the high-dose administration group of the present disclosure, 0.3 mg / g body weight of BPA-Fr was administered by inhalation to BALB / c nude mice with lung tumors. BPA-Fr was inhaled for about 6 to 8 minutes and allowed to be absorbed in the mice for 2 hours. Subsequently, ICP-MS (Thermo Fisher Scientific iCAP TQ) was used to measure 10 The concentration of B in lung tumor tissue 10The concentration of B is 1782.96 ppm, while the concentration in normal lung tissue is 51.42 ppm. The calculated T / N ratio is 34.67, indicating that it meets the minimum clinical treatment requirement of a T / N ratio greater than 2.5, as shown in Table 1. Therefore, compared to the minimum T / N ratio required for clinical treatment, the present disclosure can achieve the effect of promoting a higher T / N ratio of a boron source in an individual.

[0061] Table 1. Boron-10 uptake and T / N ratio in lung and normal lung tissue by high-dose inhalation administration (BPA-Fr clinical standard: T / N ratio>2.5) Experimental Group High dose group - Test 1 Accumulated boron-10 concentration in lung tumors (ppm) 1782.96 Accumulated boron-10 concentration in normal lung tissue (ppm) 51.42 T / N Ratio 34.67

[0062] *T / N ratio (boron-10) = lung tumor (ppm) / normal lung tissue (ppm)

[0063] also, Figure 3B and Figure 3D The results showed that compared with the control group and intraperitoneal injection, the inhalation administration method can absorb aerosolized BPA-Fr faster; or, under the same time, the absorption rate of aerosolized BPA-Fr is better than that of intraperitoneal injection.

[0064] In terms of inhalation administration, when a living body inhales the drug from the lungs, it will settle in the alveoli, and the microvessels above the alveoli will absorb the drug, so that the drug enters the tumor or healthy normal cells in the lungs, and gradually enters the blood vessels, and finally circulates to the blood throughout the body. The BPA-Fr drug will eventually be converted into boron-10 for measurement, representing the level of drug content in cells or blood; from the perspective of cancer treatment or diagnosis, the more boron-10 accumulates in tumors, the less boron-10 accumulates in normal cells or blood, the better. Figure 3A It shows that after inhalation of the same dose of aerosolized BPA-Fr drug in living bodies, the concentration of boron-10 in tumor cells and normal cells changes over time. Figure 3C The results show that after inhaling the same dose of aerosolized BPA-Fr in vivo, the concentration of intracellular boron-10 in tumor cells and blood changes over time. Figure 3A and Figure 3C It can be seen that after inhalation of aerosolized BPA-Fr drugs in vivo, relatively high boron-10 accumulation in tumors and relatively low boron-10 accumulation in normal cells or blood can be achieved within a very short period of time (5 to 10 minutes), showing the advantages of the present disclosure in treatment or diagnosis. The above description is only a preferred embodiment of the present invention. All equivalent changes and modifications made according to the scope of the patent application of the present invention should fall within the scope of the present invention.

Claims

1. A radiotherapy system comprising: Neutron receptors; an atomizing device for aerosolizing the neutron acceptor; and Energy beam generator.

2. The radiation therapy system of claim 1, wherein: The energy beam generator is a neutron beam generator, and the neutron receptor comprises an element that can be triggered or activated by neutron irradiation.

3. The radiation therapy system of claim 1, wherein: The neutron receptor is labeled with a radionuclide.

4. The radiation therapy system of claim 3, wherein: The neutron acceptor is a boron source or a gadolinium source, and the radionuclide is selected from 18 F. 15 O. 13 N. 11 C. 67 Ga, 99m Tc, 123 I. 124 I. 125 I. 131 I. 201 Tl and 111 At least one of the group consisting of In.

5. A use of a neutron receptor for preparing a drug for treating cancer in an individual in need thereof, wherein: The neutron receptor is aerosolized and comprises an element that can be triggered or activated by neutron irradiation, and the individual is subjected to neutron irradiation.

6. The use according to claim 5, wherein The cancer is lung cancer.

7. The use according to claim 5, wherein The neutron receptor is labeled with a radionuclide.

8. A use of a radioactive agent for preparing a drug for diagnosing cancer, comprising: administering an effective amount of the radioactive agent to a subject in need thereof, wherein the radioactive agent is aerosolized; and Receives energy beam signal from the individual.

9. The use according to claim 8, wherein The cancer is lung cancer.

10. The use according to claim 8, wherein The radioactive agent comprises a neutron receptor labeled with a radionuclide, and the neutron receptor comprises an element that can be triggered or activated by neutron irradiation.

11. A method for delivering neutron receptors to an individual during radiation therapy, comprising: aerosolizing the neutron receptor, wherein The neutron receptor comprises an element that can be triggered or activated by neutron irradiation; and An effective amount of the neutron acceptor is administered to the individual.

12. The method of claim 11, further comprising irradiating the subject with neutrons, and wherein: The aerosolized neutron receptor is administered by inhalation to the respiratory system of the individual, the individual has lung cancer, and the radiation therapy is neutron capture therapy.

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